The overall objective of our current and proposed studies is to understand how androgens and estrogens act either antagonistically or in concert to regulate mechanisms responsible for prostate growth differentiation. We propose to study the differential response of regressed prostatic epithelium from castrated and hypophysectomized dogs to several natural androgens and an estrogen, administered separately and in combination. In this investigation we will specify those morphological features of the responding epithelial cells and patterns of sex-hormone uptake, retention and metabolism by the affected gland that will distinguish androgen- from estrogen-controlled differentiation and antagonistic from synergistic actions on regulation of coordinated growth. We propose to investigate cell-surface alterations in non-junctional plasma membranes as well as intercellular junctions in hormonally-modified prostatic epithelium. We shall apply the experience gained with the canine model to a study of human prostate carcinoma in order to explore the differential sex-hormone responsiveness of the neoplastic cells. To accomplish these objectives we shall utilize the following investigative techniques: 1) electron microscopy: standard thin-sectioning, special procedures for preserving and enhancing contrast of cell coats, freeze-cleave replication for detailed examination of internal aspects of cell membranes. Electron micrographs will be analyzed using qualitative and morphometric criteria; 2) organ culture: for studying the uptake and disposition of labeled sex steroids in atrophied and hormone-stimulated regressed prostate; and 3) thaw-mount autoradiography: for visualizing sex-radiosteroid location in the various cell components of explants of atrophied and hormonally-modified prostate, with parallel autoradiographic 3H-thymidine labeling.